Abstract
Background
Non-inferiority and equivalence trials aim to determine whether a new treatment is good enough (non-inferior) or as good as (equivalent to) another treatment. To inform the decision about non-inferiority or equivalence, a margin is used. We aimed to identify the current methods used to determine non-inferiority or equivalence margins, as well as the main challenges and suggestions from trialists.
Methods
We developed an online questionnaire that included both closed and open-ended questions about methods to elicit non-inferiority or equivalence margins, underlying principles, and challenges and suggestions for improvement. We recruited trialists with experience of determining a margin by contacting corresponding authors for non-inferiority or equivalence trials. We used descriptive statistics and content analysis to identify categories in qualitative data.
Results
We had forty-one responses, all from non-inferiority trials. More than half of the trials were non-pharmacological (n = 21, 51%), and the most common primary outcome was clinical (n = 29, 71%). The two most used methods to determine the margin were as follows: a review of the evidence base (n = 27, 66%) and opinion seeking methods (n = 24, 59%). From those using reviews, the majority used systematic reviews or reviews of multiple RCTs to determine the margin (n = 17, 63%). From those using opinion seeking methods, the majority involved clinicians with or without other professionals (n = 19, 79%). Respondents reported that patients’ opinions on the margin were sought in four trials (16%). Median confidence in overall quality of the margin was 5 out of 7 (maximum confidence); however, around a quarter of the respondents were “completely unconfident” that the margin reflected patient’s views. We identified “stakeholder involvement” as the most common category to determine respondent’s confidence in the quality of the margins and whether it reflected stakeholder’s views. The most common suggestion to improve the definition of margins was “development of methods to involve stakeholders,” and the most common challenge identified was “communication of margins.”
Conclusions
Responders highlighted the need for clearer guidelines on defining a margin, more and better stakeholder involvement in its selection, and better communication tools that enable discussions about non-inferiority trials with stakeholders. Future research should focus on developing best practice recommendations.
Non-inferiority and equivalence trials aim to determine whether a new treatment is good enough (non-inferior) or as good as (equivalent to) another treatment. To inform the decision about non-inferiority or equivalence, a margin is used. We aimed to identify the current methods used to determine non-inferiority or equivalence margins, as well as the main challenges and suggestions from trialists.
Methods
We developed an online questionnaire that included both closed and open-ended questions about methods to elicit non-inferiority or equivalence margins, underlying principles, and challenges and suggestions for improvement. We recruited trialists with experience of determining a margin by contacting corresponding authors for non-inferiority or equivalence trials. We used descriptive statistics and content analysis to identify categories in qualitative data.
Results
We had forty-one responses, all from non-inferiority trials. More than half of the trials were non-pharmacological (n = 21, 51%), and the most common primary outcome was clinical (n = 29, 71%). The two most used methods to determine the margin were as follows: a review of the evidence base (n = 27, 66%) and opinion seeking methods (n = 24, 59%). From those using reviews, the majority used systematic reviews or reviews of multiple RCTs to determine the margin (n = 17, 63%). From those using opinion seeking methods, the majority involved clinicians with or without other professionals (n = 19, 79%). Respondents reported that patients’ opinions on the margin were sought in four trials (16%). Median confidence in overall quality of the margin was 5 out of 7 (maximum confidence); however, around a quarter of the respondents were “completely unconfident” that the margin reflected patient’s views. We identified “stakeholder involvement” as the most common category to determine respondent’s confidence in the quality of the margins and whether it reflected stakeholder’s views. The most common suggestion to improve the definition of margins was “development of methods to involve stakeholders,” and the most common challenge identified was “communication of margins.”
Conclusions
Responders highlighted the need for clearer guidelines on defining a margin, more and better stakeholder involvement in its selection, and better communication tools that enable discussions about non-inferiority trials with stakeholders. Future research should focus on developing best practice recommendations.
| Original language | English |
|---|---|
| Article number | 1021 |
| Number of pages | 10 |
| Journal | Trials |
| Volume | 23 |
| DOIs | |
| Publication status | Published - 16 Dec 2022 |
Bibliographical note
FundingBG was supported to develop this research by the Wellcome Trust Institutional
Strategic Support Fund at the University of Aberdeen. NA was supported
by the Endeavour Scholarship Scheme (Malta). Project part-fnanced by the
European Social Fund Operational Programme II – European Structural and
Investment Funds 2014-2020. The Health Services Research Unit is funded by
the Chief Scientist Ofce of the Scottish Government Health and Social Care
Data Availability Statement
Data is available from the authors upon reasonable request.Keywords
- non-inferiority trials
- elicitation methods
- opinion seeking
- margin justification
- evidence-based